Continuing exploration of the total chemical synthesis and biological evaluation of potentially anticancer chemotherapeutic members of the ellagitannin family of secondary plant metabolites is proposed. Specifically, concise and sterorational syntheses of the complex dimeric ellagitannins geraniin (DNA topoisomerase II inhibitor), and chebulagic acid (DNA topoisomerase I inhibitor) are planned. These efforts will exploit new synthetic methodology developed in-house for the preparation of the hexahydroxydiphenoyl (HHDP) and dehydrohexahydroxydiphenoyl (DHHDP) moieties featured in these target molecules. Characterization of the immunomodulatroy properties of ellagitannins, gallotannins, and analogs available through syntheses is will continue. Mechanism-of-action investigations at both the molecular and cellular level, coupled with structure/activity studies are designed to reveal the basis for both up-regulation and down - regulation of cytokine (IL-1Beta, TNFAlpha) secretion by certain tannins. Appreciation of the molecular-level details responsible for either triggering or suppressing cytokine release may serve as the basis for designing ellagitannin-inspired chemotherapeutic agents for disease as diverse as cancer septic shock, and cachexia. Finally new strategies for diasteroselective biaryl astropisomer assembly within the context of synthesis efforts directed toward the potent cytotoxic agent diazonamide A will extend current art in this area